In these investigation, a goal is to develop fundamental understandings of the relationships between electrophysiological activity and energy conservation by means of in situ monitoring of each of these in intact mammalian brain tissues. The second objective is to employ these understandings of CNS metabolism to define the mechanisms by which certain pharmacological agents act in the central nervous system. By these means, new tools will be established for pharmacological studies under in situ conditions to directly relate drug effects with the cellular mechanisms by which they are produced. The necessity for this approach is underscored by recent reports from this line of research indicating that metabolism in intact neuronal tissues differs from that expected from extrapolation of data from mitochondria isolated in vitro. Our reports show that there is a continuum of dependency of electrophysiological activity on oxidative metabolism which, in turn, shows a continuum of dependency on the supply of oxygen.